Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis

Joseph E. Maakaron; Mei Jie Zhang; Karen Chen; Sunil Abhyankar; Vijaya Raj Bhatt; Saurabh Chhabra; Najla El Jurdi; Sherif S. Farag; Fiona He; Mark Juckett; Marcos de Lima; Navneet Majhail; Marjolein van der Poel; Ayman Saad; Bipin Savani; Celalettin Ustun; Edmund K. Waller; Mark Litzow; Partow Kebriaei; Christopher S. Hourigan; Wael Saber; Daniel Weisdorf

doi:10.1038/s41409-022-01650-5

Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis

Joseph E. Maakaron, Mei Jie Zhang, Karen Chen, Sunil Abhyankar, Vijaya Raj Bhatt, Saurabh Chhabra, Najla El Jurdi, Sherif S. Farag, Fiona He, Mark Juckett, Marcos de Lima, Navneet Majhail, Marjolein van der Poel, Ayman Saad, Bipin Savani, Celalettin Ustun, Edmund K. Waller, Mark Litzow, Partow Kebriaei, Christopher S. HouriganWael Saber, Daniel Weisdorf

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

Original language	English (US)
Pages (from-to)	911-917
Number of pages	7
Journal	Bone marrow transplantation
Volume	57
Issue number	6
DOIs	https://doi.org/10.1038/s41409-022-01650-5
State	Published - Jun 2022

Bibliographical note

Funding Information:
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV.

Funding Information:
Daniel Weisdorf reports grants from FATE Therapeutics, grants from Incyte, outside the submitted work. Christopher S Hourigan reports other from Sellas, outside the submitted work. Joseph E Maakaron reports other from CRISPR, other from FortySeven Inc., other from TALARIS, outside the submitted work. Marcos de Lima reports grants from Pfizer grants from Celgene, personal fees from Kadmon personal fees from Pfizer, personal fees from Incyte, personal fees from BMS, outside the submitted work. Vijaya Raj Bhatt reports personal fees from Agios, grants and personal fees from Incyte, personal fees from Takeda, personal fees from Partner Therapeutics, personal fees from Omeros, grants and personal fees from Abbvie, grants from Jazz, grants from National Marrow Donor Program, other from Oncoceutics, personal fees from Partnership for health analytic research, LLC, grants and other from Pfizer, personal fees from CSL Behring, grants from Tolero Pharmaceuticals, personal fees from Rigel Pharmaceuticals, other from Novartis, personal fees from Genentech, outside the submitted work. Ayman Saad reports personal fees from Magenta Therapeutics, personal fees from Incyte Pharmaceuticals, personal fees from CareDx, outside the submitted work. Partow Kebriaei reports grants from Amgen, grants from Ziopharm, other from Kite, other from Novartis, other from Jazz, other from Pfizer, outside the submitted work. Celalettin Ustun reports not relevant, but honoria from Novartis and Blueprint for attending advisory board meeting. Fiona He reports personal fees from Magenta Therapeutics, outside the submitted work. Sunil Abhyankar reports other from Incyte Corporation, other from Therkos, outside the submitted work. Navneet Majhail reports personal fees from lncyte, personal fees from Anthem, Inc., personal fees from Nkarta, personal fees from Mallinckrodt, outside the submitted work.

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© 2022, The Author(s), under exclusive licence to Springer Nature Limited.

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Journal Article
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Research Support, Non-U.S. Gov't

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10.1038/s41409-022-01650-5

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Maakaron, J. E., Zhang, M. J., Chen, K., Abhyankar, S., Bhatt, V. R., Chhabra, S., El Jurdi, N., Farag, S. S., He, F., Juckett, M., de Lima, M., Majhail, N., van der Poel, M., Saad, A., Savani, B., Ustun, C., Waller, E. K., Litzow, M., Kebriaei, P., ... Weisdorf, D. (2022). Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis. Bone marrow transplantation, 57(6), 911-917. https://doi.org/10.1038/s41409-022-01650-5

Maakaron, JE, Zhang, MJ, Chen, K, Abhyankar, S, Bhatt, VR, Chhabra, S, El Jurdi, N, Farag, SS, He, F , Juckett, M, de Lima, M, Majhail, N, van der Poel, M, Saad, A, Savani, B, Ustun, C, Waller, EK, Litzow, M, Kebriaei, P, Hourigan, CS, Saber, W & Weisdorf, D 2022, 'Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis', Bone marrow transplantation, vol. 57, no. 6, pp. 911-917. https://doi.org/10.1038/s41409-022-01650-5

@article{0cfdaf1416e84c919f31333598337271,

title = "Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis",

abstract = "Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.",

author = "Maakaron, {Joseph E.} and Zhang, {Mei Jie} and Karen Chen and Sunil Abhyankar and Bhatt, {Vijaya Raj} and Saurabh Chhabra and {El Jurdi}, Najla and Farag, {Sherif S.} and Fiona He and Mark Juckett and {de Lima}, Marcos and Navneet Majhail and {van der Poel}, Marjolein and Ayman Saad and Bipin Savani and Celalettin Ustun and Waller, {Edmund K.} and Mark Litzow and Partow Kebriaei and Hourigan, {Christopher S.} and Wael Saber and Daniel Weisdorf",

note = "Funding Information: The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV. Funding Information: Daniel Weisdorf reports grants from FATE Therapeutics, grants from Incyte, outside the submitted work. Christopher S Hourigan reports other from Sellas, outside the submitted work. Joseph E Maakaron reports other from CRISPR, other from FortySeven Inc., other from TALARIS, outside the submitted work. Marcos de Lima reports grants from Pfizer grants from Celgene, personal fees from Kadmon personal fees from Pfizer, personal fees from Incyte, personal fees from BMS, outside the submitted work. Vijaya Raj Bhatt reports personal fees from Agios, grants and personal fees from Incyte, personal fees from Takeda, personal fees from Partner Therapeutics, personal fees from Omeros, grants and personal fees from Abbvie, grants from Jazz, grants from National Marrow Donor Program, other from Oncoceutics, personal fees from Partnership for health analytic research, LLC, grants and other from Pfizer, personal fees from CSL Behring, grants from Tolero Pharmaceuticals, personal fees from Rigel Pharmaceuticals, other from Novartis, personal fees from Genentech, outside the submitted work. Ayman Saad reports personal fees from Magenta Therapeutics, personal fees from Incyte Pharmaceuticals, personal fees from CareDx, outside the submitted work. Partow Kebriaei reports grants from Amgen, grants from Ziopharm, other from Kite, other from Novartis, other from Jazz, other from Pfizer, outside the submitted work. Celalettin Ustun reports not relevant, but honoria from Novartis and Blueprint for attending advisory board meeting. Fiona He reports personal fees from Magenta Therapeutics, outside the submitted work. Sunil Abhyankar reports other from Incyte Corporation, other from Therkos, outside the submitted work. Navneet Majhail reports personal fees from lncyte, personal fees from Anthem, Inc., personal fees from Nkarta, personal fees from Mallinckrodt, outside the submitted work. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

month = jun,

doi = "10.1038/s41409-022-01650-5",

language = "English (US)",

volume = "57",

pages = "911--917",

journal = "Bone marrow transplantation",

issn = "0268-3369",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Age is no barrier for adults undergoing HCT for AML in CR1

T2 - contemporary CIBMTR analysis

AU - Maakaron, Joseph E.

AU - Zhang, Mei Jie

AU - Chen, Karen

AU - Abhyankar, Sunil

AU - Bhatt, Vijaya Raj

AU - Chhabra, Saurabh

AU - El Jurdi, Najla

AU - Farag, Sherif S.

AU - He, Fiona

AU - Juckett, Mark

AU - de Lima, Marcos

AU - Majhail, Navneet

AU - van der Poel, Marjolein

AU - Saad, Ayman

AU - Savani, Bipin

AU - Ustun, Celalettin

AU - Waller, Edmund K.

AU - Litzow, Mark

AU - Kebriaei, Partow

AU - Hourigan, Christopher S.

AU - Saber, Wael

AU - Weisdorf, Daniel

N1 - Funding Information: The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV. Funding Information: Daniel Weisdorf reports grants from FATE Therapeutics, grants from Incyte, outside the submitted work. Christopher S Hourigan reports other from Sellas, outside the submitted work. Joseph E Maakaron reports other from CRISPR, other from FortySeven Inc., other from TALARIS, outside the submitted work. Marcos de Lima reports grants from Pfizer grants from Celgene, personal fees from Kadmon personal fees from Pfizer, personal fees from Incyte, personal fees from BMS, outside the submitted work. Vijaya Raj Bhatt reports personal fees from Agios, grants and personal fees from Incyte, personal fees from Takeda, personal fees from Partner Therapeutics, personal fees from Omeros, grants and personal fees from Abbvie, grants from Jazz, grants from National Marrow Donor Program, other from Oncoceutics, personal fees from Partnership for health analytic research, LLC, grants and other from Pfizer, personal fees from CSL Behring, grants from Tolero Pharmaceuticals, personal fees from Rigel Pharmaceuticals, other from Novartis, personal fees from Genentech, outside the submitted work. Ayman Saad reports personal fees from Magenta Therapeutics, personal fees from Incyte Pharmaceuticals, personal fees from CareDx, outside the submitted work. Partow Kebriaei reports grants from Amgen, grants from Ziopharm, other from Kite, other from Novartis, other from Jazz, other from Pfizer, outside the submitted work. Celalettin Ustun reports not relevant, but honoria from Novartis and Blueprint for attending advisory board meeting. Fiona He reports personal fees from Magenta Therapeutics, outside the submitted work. Sunil Abhyankar reports other from Incyte Corporation, other from Therkos, outside the submitted work. Navneet Majhail reports personal fees from lncyte, personal fees from Anthem, Inc., personal fees from Nkarta, personal fees from Mallinckrodt, outside the submitted work. Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2022/6

Y1 - 2022/6

N2 - Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

AB - Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

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DO - 10.1038/s41409-022-01650-5

M3 - Article

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VL - 57

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JO - Bone marrow transplantation

JF - Bone marrow transplantation

IS - 6

ER -

Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis

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